The coupling of nicotinamide adenine dinucleotide (NAD⁺) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD⁺ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD⁺ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD⁺ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD⁺ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD⁺ and sirtuins in aging/longevity control.

烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 分解和蛋白质脱酰化的偶联是称为“sirtuins”的蛋白质家族的一个独特特征。^{NAD +}和 sirtuins之间的这种密切联系有着古老的起源，并提供了将能量代谢的调节转化为多种生物体的衰老和寿命控制的机制基础。尽管 sirtuin 研究领域经历了激烈的争议，但最近越来越多的研究已经平息了这些争议，并充分确立了 sirtuin 作为进化上保守的衰老/长寿调节剂的重要性。NAD ^{+之间的紧密联系}和 sirtuins 在几个不同的水平上受到调节，进一步增加了它们在代谢和衰老/寿命控制中的协调性。有趣的是，已经证明 NAD ⁺可用性随着年龄的增长而降低，降低了沉默调节蛋白的活性，并在细胞水平上影响细胞核和线粒体之间的通讯，以及在全身水平上影响下丘脑和脂肪组织之间的通讯。这些动态的细胞和全身过程可能有助于与年龄相关的功能衰退的发展和衰老疾病的发病机制。为了缓解这些与年龄相关的问题，补充关键的 NAD ⁺中间体目前备受关注。^{在这篇评论文章中，我们将总结 NAD +}和 sirtuins 在衰老/长寿控制中的密切联系的这些重要方面。